The Role of the Protein C-Thrombomodulin System in Physiologic Anticoagulation During Cardiopulmonary Bypass

Abstract

Changes in the protein C-thrombomodulin (PC-TM) system in relation to other coagulofibrinolytic parameters were examined in 25 patients undergoing open heart surgery. Although all patients were given heparin, a decrease in antithrombin III (ATIII) and progressive increase in thrombin-ATIII complex (TAT) and fibrinopeptide A (FPA) levels were noted during cardiopulmonary bypass, which indicated that heparinization did not completely inhibit the formation of thrombin and its function. C1-inactivator (INA) resistant fibrinolytic activity increased markedly during CPB, in parallel with the change of tissue plasminogen activator antigen (t-PA;Ag), which indicates that fibrinolytic activity during CPB is mainly of extrinsic origin caused by t-PA. Protein C antigen (PC;Ag), protein S antigen (PS;Ag), and thrombomodulin antigen (TM;Ag) were all decreased significantly during CPB. This is considered to reflect the activation and consumption of the PC-TM system in response to generated thrombin. Furthermore, enhancement of the extrinsic fibrinolytic system is easily explained by the action of activated PC, which counteracts plasminogen activator inhibitor (PAI-1), to cause enhancement of t-PA activity.